Dental preparations

ABSTRACT

DENTAL PREPARATION CONTAINING A FLUORIDE AND A POLISHING ABRASIVE AGENT, A MIXTURE OF MAGNESIUM AMMONIUM PHOSPHATE AND CALCIUM HYDROGEN PHOSPHATE.

United States Patent 3,655,867 DENTAL PREPARATIONS Ludwig Schoernig,Frankfurt am Main, Germany, assignor to Farbwerke HoechstAktiengesellschatt vormals Meister Lucius & Bruning, Frankfurt am Main,Germany No Drawing. Continuation-impart of application Ser. No. 601,312,Dec. 13, 1966. This application May 1, 1970,

Ser. No. 33,916

Int. Cl. A6lk 7/16 US. Cl. 424--52 1 Claim ABSTRACT OF THE DISCLOSUREDental preparation containing a fluoride and a polishing abrasive agent,a mixture of magnesium ammonium phosphate and calcium hydrogenphosphate.

This patent application is a continuation-in-part application of patentapplication Ser. No. 601,312 filed Dec. 13, 1966, now abandoned.

The present invention relates to dental preparations which containfluorides and, as abrasive and polishing agents, magnesium ammoniumphosphate and calcium hydrogen phosphate.

The term dental preparation as used herein is intended to encompass in ageneral sense tooth pastes, tooth powders and tooth soaps.

Tooth pastes generally consist of an abrasive and polishing agent, anaqueous solution of humectants and binders, tensides, coloring andflavoring substances, and other additives which may have antiseptic,deodorizing, bleaching, astringent and anticarious action.

Tooth powders generally consist of the same basic substances as toothpastes but they do not contain the aqueous solution of humectants andbinders.

Tooth soaps generally contain a polishing agent, tensides, soaps,flavoring and coloring substances and only a small amount of humectants.

As abrasive and polishing agents, there are generally used sparinglysoluble substances such, for example, as those described in Ullmann,Enzykl. techn. Chemie, (Urban and Schwarzenberg, Munchen-Berlin), 3rdEdition (1958, volume 10, pages 714-716 and 718).

For the usability of a dental preparation intended for permanent use,the abrasiveness of the abrasive and polishing agent contained in thepreparation is of decisive importance. It depends on the size and thehardness of the particles of the abrasive and polishing agent.

Powders having coarse particles feel sore and sandy in teeth cleaning.They also affect the gum, because coarse and in addition, sparinglysoluble powder residues may remain behind dental preparations withodontolithe removing action. For teeth which are free from dentalcalculus, these preparations are less suitable.

As regards the calcium phosphates, calcium pyrophosphate and calciumhydrogen phosphate are also used as abrasive and polishing agents.Calcium pyrophosphate has a hard grain and is strongly abrasive. It isvery difficultly soluble, which fact leads to disagreeable secondaryreactions if this compound is not completely removed from the dentalarea. In contradistinction to the pyrophosphate, the calcium hydrogenphosphate has a very soft grain. -It is only very weakly abrasive evenif it is not ground to a microfine crystaline powder and has still agood and effective cleaning power.

Magnesium salts too are used as abrasive agents in dental preparations:magnesium carbonate is quite abrasive, and magnesium ammonium phosphateis, even in unground state, a very mild polishing agent with a goodcleaning effect.

Patented Apr. 11, 1972 ice Regarding the harmlessness of a teethcleaning preparation, it is of importance to know the dependence of theabrasive action on the surface of the teeth on the hardness and the sizeof the grains of the polishing agent. Numerous methods and devices formeasuring the abrasion are known, which permit to determine and tocompare extent of the polishing action. A simple and suitable testmethod consists in introducing an aqueous suspension of the polishingagent or of the corresponding dental preparation into a metal cup, forexample, a copper cup, and to allow a round brush to rotate and to slidealong the wall. The amount of metal abraded from the wall of the cup isthen a measure of the abrasion. This apparatus permits the gradualdetermination of the abrasiveness of abrasive agents and,simultaneously, the determination of the influence of the grain size.Just as regards the grain size, there have been found quite considerabledifferences in abrasiveness, for example those described above forcalcium carbonate.

An important requirement which abrasive and polishing agents in dentalpreparations must meet is their compatibility with the other componentsand the active substances of the dental preparations, for example, theircompatibility with fluorides which are of increasing interest andimportance as additives having anticarious action.

The human organism is able to excrete the fluorine it has taken up, in adaily quantity of about 2.5 mg. This dose is, therefore, considered theharmless and tolerated dose and it is generally contained in about 1 g.of a fluorine-containing tooth paste. On the average, about 1.5 g. oftooth paste are used for tooth cleaning. This amount thus contains about34 mg. of fluorine. Only a negligible part thereof is taken up by thestomach. Hence the extensive prevention of dental caries is to beattributed above all to a local action in the mouth. If about 20-30 ml.of water are used during tooth cleaning, which is in general the case, afluorine concentration during tooth cleaning of about meg. (p.p.m.) perml. of mouth liquid can be expected. In order to be able to react withthe surface of the tooth within the short period during which the teethare cleaned, the fluorine must be in the dissolved state. It must not bebound by the abrasive or polishing agent or if bound then it should bebound to a very small extent only.

However, some, especially microfine polishing agents, bind fluorine ionseasily and rapidly. For example, calcium carbonate forms with alkalimetal fluoride a sparingly soluble calcium fluoride. In additionthereto, the said fluoride is adsorbed by calcium carbonate. The degreeof adsorption depends on the pH-value of the suspension. If alkali metalcarbonates are added, a greater quantity of fluorine ions remain behindin the aqueous solution, according to the self-establishing balance.Tooth pastes of this type, however, have a strong alkaline action, whichaffects the mucuous membrane of the mouth on prolonged application.Magnesium carbonate also adsorbs alkali metal fluoride. When sodiumpolyphosphate is used as abrasive agent in dental preparations, nolinkage with the fluorine takes place. However, the polyphosphate is inmost cases used in combination with calcium pyrophosphate. The latter iscompatible with fluorine ions, because it is extremely sparinglysoluble. But sodium polyphosphate as well as calcium pyrophosphate arenot satisfactory in dental preparations for permanent use, because oftheir above described abrasive action.

For the anticarious action of a dental preparation, it is important thatthe dental preparation contains calcium and phosphate together. Thepresence of calcium is of considerable importance also with regard tothe adaptation of the preparation to the calcium ion content of thesaliva. With a view to obtaining a thorough cleaning effect and a verymild abrasive action and, at the same time, a good anticarious elfect,it seemed interesting to combine in a dental preparation calciumhydrogen phosphate which also has a good anticarious action when 4neither turn acidic nor solidify upon storage, so that they areunusable, and when used do not show a reduction of the concentration ofdissolved fluorine in the mouth liquid to a therapeutically ineifectivevalue.

MgNH4PO4.6H2O, Molar ratio, Weight ratio Fluorine Stability of the paste03111 0421120, mols m Ca/Mg of CazMg salt ions, mols pH change at roomtemperature 0.219 l. 334 0. 164 :90 1 After 1 year O.3 units Paste after1 year unchanged. (Constant viscosity within the limit of error.) 12. 80.423 22. 2:77. 8 1 .do Do. 10. 5 0.495 25:75 1 do Do. 8. 11 1. 42 49:51-do Do.

3. 9 4. 52 75.4:24. 6 1 do Do. 0. 307 70. 4 98:2 1 do Do. 0.078 285 99.510.5 1 do Do. 100:0 1 pH 7.41 ediately after Paste solid already alterthe manufacture. pH 4.3 4 Weeks. after one year.

applied orally, with a fluoride, for example, an alkali This behaviourwhich 15 evident from the table was not metal fluoride or an alkalineearth metal fluoride. In corresponding tests, the following results wereobtained.

Tooth pastes which, for example, contained about 40% of calcium hydrogenphosphate and 0.2% of fluorine (as sodium fluoride) showed at thebeginning a neutral reaction (pH 7.2-7.4), but became then acidic (pH4.2-4.4). Upon storage, they hardened and could not be pressed out fromthe tubes and were thus unusable. From the calcium hydrogen phosphateand the fluoride, for example, an alkali metal fluoride, there formedfluorine-apatite, sodium dihydrogen phosphate and free phospheric acid.

When, for example, 0.5 mol of calcium hydrogen phosphate and 0.1 mol ofsodium fluoride were suspended in 0.3 l. of water, the soluble fluorinerapidly disappeared from the liquid. At 37 C., 55.4% of the fluorineused were found after 3 minutes, 71% after 5 minutes and 95.4% werefound after 10 minutes in the deposit.

In this reaction, the pH- value of the suspension fell from 7.4 to 2.2.An attempt to increase the portion of soluble fluorine by alkalinizationwith sodium carbonate or sodium hydroxide, as described above forcalcium carbonate and sodium fluoride, had the contrary result: when asuspension containing calcium hydrogen phosphate and sodium fluoride inthe usual ratio for tooth pastes (40% of abrasive and polishing agentand 0.2% of fluorine) and in the concentration expected during toothcleaning, was adjusted to a pH-value of 7-7.2 by dropwise addition ofdilute sodium hydroxide solution, the fluorine was bound at 38 C. withina short time by the polishing and abrasive body. Only 0.8 p.p.m. ofdissolved fluorine were found in the filtrate. When the pH-value wasadjusted to 8-8.5, only 0.2 p.p.m. of soluble fluorine could be detectedin the filtrate. Hence, the quantity of fluorine given off by theapatite decreases considerably with increasing pH- value.

Not only the addition of alkali, but also calcium hydro gen phosphatereduces the concentration of dissolved fluorine in an apatitesuspension. For example, in a fluorine apatite suspension containingonly 10% of calcium hydrogen phosphate, calculated on the apatite, 0.6ppm. were found at 23 C., and at 40 C. only 0.9 p.p.m. of dissolvedfluorine were found in the filtrate. Thus, the calcium hydrogenphosphate largely binds the small amount of fluorine given oif by thefluorine apatite. Dental preparations, however, whose content of solublefluorine is below that of a fluorine apatite suspension, will not have atherapeutic action.

Now, we have found that, surprisingly, it is possible to add calciumhydrogen phosphate to dental preparations, preferably tooth pastes,which contain a soluble fluoride in a therapeutically effective dosage,in the presence of magnesium ammonium phosphate as the abrasive andpolishing body; the dental preparations thus prepared to be expected,since it was rather to be expected that in the paste which owing to themagnesium ammonium phosphate showed a weakly alkaline or neutralreaction or in its aqueous suspension formed during tooth cleaning, thefluoride would be bound by the calcium hydrogen phosphate to form asparingly soluble fluorine apatite and that the concentration of solublefluorine would be below the therapeutically effective level, which wouldhave been expected especially with an excess addition of calciumhydrogen phosphate.

Salulzky (U.S. Pat. 3,155,454) discloses that magnesium ammoniumphosphate may react with calcium ions to form insoluble calcium ammoniumphosphate and magnesium ions. That this reaction cannot explain thepresent invention can be seen from the fact, that the tooth pastescontaining fluoride ions with a ratio of calcium: magnesium of more than1 do neither become solid nor acid (cf. the above table). It issurprising that even a very small amount of magnesium ammonium phosphateof about 2% or even less as for example of 0.5% results in a tooth pastewhich does not become solid whereas a paste containing no magnesiumammonium phosphate is solid (and acid) already after 4 weeks.

Since, according to the present invention, the fluorine remains solublein a therapeutically effective concentration, the physiologicallyharmless dose of about l-3 mg. of fluorine, preferably 2 mg. offluorine, for 1 g. of tooth paste, is sufiicient. As fluorides which maybe used according to the invention, there may be mentioned, for example,alkaline earth metal fluorides, preferably alkali metal fluorides such,for example, as sodium fluoride, potassium fluoride or magnesiumfluoride. The fluorides may also be used in admixture with one anotheror in form of their double salts.

The mixing proportion of calcium hydrogen phosphate to magnesiumammonium phosphate can be varied within wide limits. In tooth pasteswhich as a rule contains 20- 60%, preferably 35-50% of abrasive andpolishing agent, the mixture of polishing and abrasive agent may becomposed of about 5-99.5% of calcium hydrogen phosphate and 95-0.5% ofmagnesium ammonium phosphate. A prepared composition of abrasive andpolishing agent comprises 20-50% of calcium hydrogen phosphate andEEO-50% of magnesium ammonium phosphate. For tooth powders, which forexample, contain up to about 95% of abrasive and polishing agent, it maybe suitable to use a greater amount of calcium hydrogen phosphate and asmaller amount of magnesium ammonium phosphate. For tooth soaps, anamount of up to about of abrasive and polishing agent is generally used.

Among the known hydrates of magnesium ammonium phosphate and calciumhydrogen phosphate, there are preferably used the magnesium ammoniumphosphate hexahydrate and the calcium hydrogen phosphate dihydrate.

In addition to the abrasive and polishing agents, the dentalpreparations of the present invention may also contain the otheradditives generally used for such purposes. Thus, for example, thedental preparations may contain humectants, for example, glycerol,sorbitol, urea, etc., dissolved in water; tooth pastes may contain suchhumectants in amounts of about 10-50%; tooth soaps may contain smalleramounts of up to about 20%. For tooth powders humectants are notnecessary. As binders, there are suitable, among others, carboxymethylcellulose, tragacanth, agar-agar, in a quantity of 0.l%, preferably0.52%. The dental preparations of the present invention can beflavoured, depending on the requirements, with a quantity of about0.54%, preferably about 1%, of essential oils. The quantity of foamingagent is suitably adjusted to the quantity of foam considered to beagreeable during usage. A quantity of about 0.3-5 of the known tensidesis generally suflicient. In tooth powders, it is not necessary to usesuch tensides.

The quantity ranges of the other ingredients, which may be added, arenot critical. If particular properties of the dental preparations are tobe obtained, the proportions of the additives may be considerablygreater or smaller. In general, however, the required components will beadded in the usual amounts, because the dental preparations of thepresent invention do not become acidic upon storage and thus do notaffect the additives, especially the flavoring agents and special activesubstances.

The dental preparations can be prepared by the methods which are usualin the production of dental preparations, for example, by the methoddescribed in Ullmann, Enzykl. techn. Chemie (Verlag Urban undSchwarzenberg, Munchen-Berlin), 3rd Edition, volume 10, page 714 et seq.

The dental preparations of the present invention, which contain fluorineand, as abrasive and polishing agents, a mixture of calcium hydrogenphosphate and magnesium ammonium phosphate, represent a considerableadvance in the art, because the preparations do not become unusable bysolidification or hardening and have a very mild abrasiveness owing totheir content of magnesium ammonium phosphate. By the addition ofcalcium hydrogen phosphate the requirement of a simultaneous presence ofcalcium and phosphate to promote anticarious activity is met and theabrasive action, especially the cleaning effect, of a paste containingonly magnesium ammonium phosphate, which has a very soft grain, isincreased and the dental preparation is adjusted in the required mannerto the calcium ion content of the saliva. Furthermore, the fluorine ionbinding effect of the calcium hydrogen phosphate is suppressed to theutmost extent, despite the weakly alkaline to almost neutral reactionwhich is adapted to the biological state of the mouth liquid, and thusprevents the concentration of dissolved fluorine falling below thetherapeutically effective value which should be at disposal during teethcleaning.

The following examples serve to illustrate the invention but they arenot intended to limit it thereto. The quantitative proportions may bevaried within the scope of the aforegoing disclosure without impairmentof the effects obtained according to the present invention.

EXAMPLE 1 29.6 g. of magnesium ammonium phosphate hexahydrate, 29.6 g.of calcium hydrogen phosphate dihydrate, 0.9 g. of potassium fluorideand 0.2. g. of flavor oil were intimately mixed in a mixing drum or in atumbling mixer.

06 g. of the tooth powder was suspended in 30 ml. of water (37 C.). Thesuspensio. showed a pH-value of 8.2.

The quantity of fluoride which remained in solution was determined inthe filtrate of the suspension, which had been shaken for one minute. 78mcg. (=microgram) of soluble fluorine were found in 1 ml. of filtrate.

A tooth powder, obtained by mixing 44.4 g. of magnesium ammoniumphosphate hexahydrate, 14.8 g. of calcium hydrogen phosphate dihydrate,0.9 g. of potassium fluoride and 0.2 g. of flavor oil, had 76 mcg. ofsoluble fluoride per ml. of filtrate (test temperature 37 C.).

Av tooth powder obtained by mixing 53.3 g. of magnesium ammoniumphosphate hexahydrate, 5.9 g. of calcium hydrogen phosphate dihydrate,0.9' g. of potassium fluoride and 0.2 g. of flavor oil, had 72 mcg. ofsoluble fluoride in the filtrate (test temperature 37 C.).

A tooth powder obtained by mixing 56.6 g. of magnesium ammoniumphosphate hexahydrate and 2.6 g. of calcium hydrogen phosphatedihydrate, 0.9 g. of potassium fluoride and 0.2 g. of flavor oil, gavemcg. of soluble fluorine per ml. of filtrate of the suspension (testtemperature 37 C.).

EXAMPLE 2 When for cleaning the teeth a greater quantity of tooth powderwas used with an equal quantity of water or the same quantity of toothpowder with a smaller quantity of water, the concentration of fluorinethat remained soluble was increased.

The following table shows the concentration of fluorine, in toothpowders with increasing calcium hydrogen phosphate contents and fallingmagnesium ammonium phosphate contents, determined in the filtrate of thesuspension which was shaken for one minute.

12 g. of tooth powder containing about 8.88 g. of abrasive and polishingagent, the composition of which may correspond to the values given inthe following table, were intimately mixed with 0.135 g. of potassiumfluoride and 0.3 g. of flavor oil. 0.92 g. of this tooth powder wassuspended in 30 ml. of water having a temperature of 37 C. and thesuspension was shaken for one minute; the quantity of dissolved fluorinewas then determined. The results are shown in the following table.

TABLE Calcium Magnesium ammohydrogen Dissolved nium phosphate,phosphate, Mixing fluorine, grams grams ratio p.p.m. pH

When the tooth powder containing 6.69 g. of magnesium ammonium phosphateand 2.23 g. of calcium hydrogen phosphate was shaken for one hour at 37C. with water, 79 p.p.m. of soluble fluorine could be detected in thefiltrate of the suspension.

The content of dissolved fluorine in the filtrate shows that a toothpowder which contains 510% of magnesium ammonium phosphate and 95-90% ofcalcium hydrogen phosphate already assures, with the usual dosage offluorine, a sufficient concentration of soluble fluorine in the mouthrinsing liquid during teeth cleaning.

The tests furthermore show that, after an addition of magnesium ammoniumphosphate, the calcium hydrogen phosphate does not bind essentialquantities of fluorine.

EXAMPLE 3 700 g. of glycerol, 50 g. of carboxymethyl cellulose, 1.25 g.of sodium salt of saccharin, 25 g. of sodium cyclamate, 25 g. ofpotassium benzoate, 22.5 g. of sodium fluoride, 250 g. of urea, 1000 g.of distilled water were thoroughly mixed in a kneader. As soon as themass was homogenous, 1750 g. of magnesium ammonium phosphate hexahydrateand 500 g. of calcium hydrogen phosphate dihydrate were added.

The mass was then kneaded for 30 minutes at a slightly reduced pressure(40-50 mm./Hg) and a mixture of 300 g. of glycerol, 100 g. of laurylsulfate, 70 g. of flavor oil and 206.25 g. of distilled water wereadded. After a further kneading for 30 minutes without application ofreduced pressure, the paste was introduced on a roller mill, aerated andfilled into tubes. The content of abrasive and polishing substance,referred to tooth paste, amounted to 45%. Directly after preparation, aviscosity of 37 7 poises was measured with a recording structuralviscosimeter.

In order to test the properties of the paste, samples thereof werestored in a refrigerator, at room temperature, and in an incubator at 40C.

After a period of 12 months, the sample stored in the refrigerator atabout 4-5" C. showed a viscosity of 438 poises. The sample stored atroom temperature showed a viscosity of 361 poises and the sample storedin the incubator at 40 C. showed to have a viscosity of 387 poises. Thesamples measured in the meantime showed the variations usual in thedetermination of the viscosity.

The pH-value of a suspension of 2.25 g. of paste in 30 ml. of wateramounted to 8.2, directly after the preparation. The paste stored in therefrigerator had a pH- value of 7.9; the sample stored at roomtemperature had a pH-value of 7.8 and the paste stored in the incubatora pH-value of 7.4.

The paste extruded from the tube was uniform, smooth and viscous withall three samples stored.

The test for the amount and the speed of formation of foam carried outwith the stored samples showed no observable difference to a freshpaste.

For determining the soluble fluorine to be expected in the mouth liquidduring teeth cleaning, 1.5 g. of paste were suspended in 20 ml. ofdistilled water and the suspension was shaken for one minute. Thesuspension was then pressed through a clarifying filter (B.K.-filter). Afreshly prepared paste showed to have 40.2 mcg. of soluble fluorine perml. of filtrate. The sample stored for 12 months at 40 C. in anincubator, showed to have a fluorine content of 34.4 mcg. per ml. offiltrate. The fluorine values of the sample stored for 12 months in arefrigerator correspond to this content of fluorine. The abrasivenessmeasured on a copper cylinder did not change in all three samples. I

A tooth paste containing only calcium hydrogen phosphate dihydrate andfluoride, but no magnesium ammonium phosphate hexahydrate, showed thefollowing behaviour:

8 COMPOSITION OF THE PASTE G. Calcium hydrogen phosphate 500 Glycerol150 Lauryl sulfate 15 Hydroxyethyl cellulose 15 Sodium benzoate 5 Urea125 Sodium fluoride 4.4 Flavor oil 16 Distilled water--Ad 1000.

The tooth paste was prepared as described above in a kneader. Theviscosity was measured shortly after the preparation and found to be 300poises. After storage for 4 weeks at room temperature (24 C. the toothpaste could no be extruded from the tube.

The pH-value of the suspension (2.25 g. of paste in 30 ml. of water)was, with a fresh paste, 7.3-7.4, after storage for 18 days 4.7 andafter 5 weeks 4.3. The pH-value then remained constant.

We claim:

1. In a dental preparation which includes calcium hydrogen phosphate anda source of soluble fluoride and which provides a therapeuticallyeflective fluoride concentration in mouth liquid, the improvedcomposition which comprises:

(a) a carrier consisting of 5% to 99.5% calcium hydrogen phosphate andto 0.5% magnesium ammonium phosphate, said percentages being by weightof total phosphates; and

(b) a physiologically harmless but therapeutically effective amount ofan alkaline metal fluoride.

References Cited UNITED STATES PATENTS 2,018,410 10/1935 McDonald et al.424-57 2,078,498 4/ 1937 Klarmann et al. 424-57 3,105,013 9/1963 Saul etal. 424--52 3,155,454 11/1964 Salutsyl et al. 23-----1 OTHER REFERENCESSagarin, Cosmetics: Science and Technology, published by IntersciencePublishers, Inc., New York, 1957, pp. 342 and 343.

RICHARD L. HUFF, Primary Examiner US. Cl. X.R. 42457 UNITED STATESPATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 6: 86? Dated April 11197 InventO1-( Ludwig fichoergig It is certified that error appears inthe above-identified patent and that said Letters Patent are herebycorrected as shown below:

In the Heading:

After "'Ser. No. 55,916" insert Claims priority, Germany, December 17,1965, F 7,950".

Signed and sealed this 18th day of July 1972.

(SEAL) Attest:

EDWARD M.FLETCHER,JR. ROBERT GOTTSCHALK Attesting Officer Commissionerof Patents 7 FORM uscoMM-Dc 60376-P69 U.5. GOVERNMENT PRINTING OFFICE 1'99 0" 356'33

